Hypoxia-induced hsa-miR-101 promotes glycolysis by targeting TIGAR mRNA in clear cell renal cell carcinoma

Xu,Xiaochao; Liu,Chao; Bao,Jinku

doi:10.3892/mmr.2017.6139

Hypoxia-induced hsa-miR-101 promotes glycolysis by targeting TIGAR mRNA in clear cell renal cell carcinoma

Authors:
- Xiaochao Xu
- Chao Liu
- Jinku Bao
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Affiliations: College of Bioindustry, Chengdu University, Chengdu, Sichuan 610106, P.R. China, College of Life Science, Leshan Normal University, Leshan, Sichuan 614000, P.R. China, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China
Published online on: January 24, 2017 https://doi.org/10.3892/mmr.2017.6139
Pages: 1373-1378

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Abstract

Increasing evidence suggests that microRNAs (miRNAs) are essential in carcinogenesis, therefore, the present study investigated the role of hsa‑miR‑101 in renal tumorigenesis and cancer development. On identification of its expression pattern, it may serve as a diagnostic biomarker for clear cell renal cell carcinoma (ccRCC). In the present study, 10 pairs of ccRCC and noncancerous tissue samples were obtained to examine whether the expression of hsa‑miR‑101 is linked to cancer. The data obtained were validated using reverse transcription‑quantitative polymerase chain reaction analysis. The levels of hsa‑miR‑101 were examined following exposure to hypoxia in ACHN and HK‑2 cells. As a predicted target, the mRNA and protein levels of TP53‑induced glycolysis and apoptosis regulator (TIGAR) were then assessed. A pcDNA‑GFP‑miR‑101 plasmid was stably transfected into ACHN and HK‑2 cells, following which the effects of hsa‑miR‑101 on the expression of TIGAR and inhibition of glycolysis were investigated. The present study also examined the association between the level of hsa‑miR‑101 and kidney tumors. It was identified that the expression level was significantly higher in the ccRCC tissues, compared with that in the corresponding noncancerous tissues. The expression values for the upregulated miRNA ranged between 4.6‑ and 67.9‑fold. On demonstrating the functional link between hypoxia and the expression of miRNAs changes in the expression of hsa‑miR‑101 were examined following hypoxia exposure in kidney tumor and non‑tumor cell lines. It was shown that hypoxia exposure significantly induced hsa‑miR‑101. The hypoxia‑induced upregulation of hsa‑miR‑101 repressed the activity of TIGAR by targeting TIGAR mRNA and promoting glycolysis. The results showed that the upregulation of hsa‑miR‑101 in ccRCC was induced by hypoxia. Its expression deceased the protein expression of TIGAR and promoted glycolysis. This regulatory pathway may represent a novel mechanism of carcinogenesis and requires further investigation.

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